Methods of Preparing Non-Alcohol Bioactive Essential Oil Mouth Rinses

ABSTRACT

The invention relates generally to liquids such as mouth rinses for the prevention and elimination of bad breath as well as for the reduction of oral microorganisms responsible for the development of dental plaque and tooth decay. In particular, the present invention relates to a method of preparing non-alcohol or reduced alcohol mouth rinses effective at preventing the above-mentioned problems.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation application which claims thebenefit of divisional application Ser. No. 15/668,775, filed Aug. 4,2017, which claims the benefit of Ser. No. 15/487,913, filed Apr. 14,2017 (now U.S. Pat. No. 9,763,863, Granted Sep. 19, 2017), which iscontinuation application of United States divisional patent applicationSer. No. 14/326,041, filed Jul. 8, 2014 (now U.S. Pat. No. 9,693,944,Granted Jul. 4, 2017), which application claims the benefit of U.S.non-provisional application Ser. No. 12/827,970 filed Jun. 30, 2010(abandoned), the complete disclosure of which is incorporated herein byreference for all purposes.

FIELD OF THE INVENTION

The invention relates generally to liquids such as mouth rinses for theprevention and elimination of bad breath as well as for the reduction oforal microorganisms responsible for the development of dental plaque andtooth decay. In particular, the present invention relates to methods ofpreparing non-alcohol or reduced alcohol mouth rinses effective atpreventing the above-mentioned problems.

BACKGROUND OF THE INVENTION

Mouth rinse or mouthwash compositions have been used by people for manyyears for the prevention of bad breath and for the elimination ofbacteria and other oral microorganisms that are responsible not only forbad breath but also tooth decay, plaque and gum diseases such asgingivitis and periodontitis. To this end, antiseptic mouthwashes in thepast have been designed to clean the oral cavity, provide fresh breathand kill these pathogenic microbes.

Leading antiseptic mouth rinses have traditionally contained alcohol(i.e., ethanol) at fairly high levels, ranging from approximately 20% upto about 30% by volume, based on the total mouthwash volume (hereinafterreferred to as “% v/v”). Alcohol is used both as a vehicle and as asolvent in which the active ingredients, and additives such asastringents, fluorides, color additives, flavor oils, and the like, canbe dissolved and then dispersed into solution. Alcohol also provides apreservative role for the mouth rinse during storage and use, andenhances the flavor oil organoleptic cues.

However, the use of high levels of alcohol may sometimes be foundunacceptable by some mouthwash users. Senior citizens have alsocomplained about problems related to gargling with such mouth rinses,and chronic exposure has been found to result in a feeling of gum “burn”resulting from the high concentrations of alcohol. It has also beenreported that alcoholic mouth rinses can result in an unpleasant “drymouth” sensation.

On the other hand, reducing the levels of alcohol in these mouth rinsecompositions can have significant disadvantages. Such disadvantagesinclude a reduction in the solubility of the mouth rinse actives and/orthe other mouth rinse ingredients.

For example, it has been found that lowering alcohol concentration(i.e., replacing the alcohol with water) in commercially available mouthrinse compositions can result in cloudy or turbid compositions. Cloudyor turbid compositions present a clear disadvantage from an aestheticpoint of view since clear mouth rinse solutions are certainly morepreferred by consumers than cloudy, turbid or otherwise heterogeneousones.

Additionally, it has been found that lower alcohol concentrations resultin a noticeable decrease in the ability of the composition to kill theoral microorganisms responsible for bad breath, plaque and gum disease.This loss in antimicrobial activity is not only due to the reduction ofalcohol as a vehicle, but also to the reduced bioavailability of thesolubilized actives.

Thymol, for example, is a well known antiseptic compound, also known asan essential oil, which is utilized for its antimicrobial activity in avariety of mouthwash or mouth rinse preparations. In particular, thymolcan be utilized in oral hygiene compositions such as mouth rinses insufficient quantities to provide desired beneficial therapeutic effects.Mouthwashes with thymol are well-known, and have been used by millionsof people for over one hundred years. They have been proven effective inkilling microbes in the oral cavity that are responsible for plaque,gingivitis and bad breath. Thymol, together with other essential oilssuch as methyl salicylate, menthol and eucalyptol, comprise the activecomponent in some antiseptic mouth rinses. These oils achieve goodefficacy although present in small amounts. Without being restricted toany specific theory, it is now believed that the efficacy and taste ofantiseptic mouth rinses may be due to the improved dispersion ordissolution of the oils and bioavailability after such dispersion ordissolution of these four active ingredients.

Obviously then, there is a substantial need for the development of areduced and/or no alcohol mouth rinses, and methods of producing them orother liquids, which are aesthetically pleasing to consumers and provideimproved dispersion or dissolution of the essential oils yet maintainthe bioavailability of the essential oils for preventing bad breath,killing oral microbes and reducing or eliminating plaque.

Therefore, an aspect of the present invention is to liquid compositionscontaining oil or oily components which have reduced turbidity orcloudiness.

Another aspect of the present invention is to provide mouth rinsecompositions which are aesthetically pleasing to consumers and provideimproved dispersion or dissolution of the essential oils yet maintainthe bioavailability of the essential oils for preventing bad breath,killing oral microbes and reducing or eliminating plaque.

SUMMARY OF THE INVENTION

In certain embodiments, the present invention relates to methods forpreparing a liquid composition or mouth rinse comprising the steps of:

-   -   a.) preparing a first premix composition comprising:        -   i. a first oil or oily component;        -   ii. optionally, a first polyol solvent, and        -   iii. optionally, a flavor;    -   b.) preparing a second premix composition comprising:        -   i. a second oil or oily component having a degree of            hydrophobicity less than the degree of hydrophobicity of the            first oil or oily component, and        -   ii. a second polyol solvent;    -   c.) preparing a third premix composition comprising:        -   i. at least one surfactant, and        -   ii. an aqueous phase comprising water;    -   d.) adding the first premix to the third premix;    -   e.) mixing the composition of step d.) until uniform and        homogeneous;    -   f.) adding the second premix to the composition of step e.) and        mixing until uniform and homogeneous;    -   g.) optionally, adding a sugar alcohol solvent; and    -   h.) optionally, mixing the composition of step g.) until uniform        and homogeneous.

In certain embodiments, the liquid composition or mouth rinse is areduced alcohol or non-alcohol composition.

In further embodiments, a method for preparing a reduced alcohol ornon-alcohol, antimicrobial mouth rinse composition is disclosed thatexhibits a high level of antimicrobial activity as measured by anM-factor greater than 0.5 (or about 0.5), optionally 1.0 (or about 1.0)optionally, 2.0 (or about 2.0), or optionally 3.0 (or about 3.0) where“M-factor” equals the log RLU value of biofilm treated with water usedas the negative control minus the log RLU value of biofilm treated withthe mouth rinse composition being tested. In addition, the oral mouthrinse compositions of this invention are clear (to the unaided humaneye) and aesthetically appealing products.

DETAILED DESCRIPTION OF THE INVENTION

The liquid or mouth rinse compositions of the present invention cancomprise, consist of, or consist essentially of the essential elementsand limitations of the invention described herein, as well any of theadditional or optional ingredients, components, or limitations describedherein. The term “comprising” (and its grammatical variations) as usedherein is used in the inclusive sense of “having” or “including” and notin the exclusive sense of “consisting only of.”

The terms “a” and “the” as used herein are understood to encompass theplural as well as the singular.

Unless otherwise indicated, all documents cited are, in relevant part,incorporated herein by reference; the citation of any document is not tobe construed as an admission that it is prior art with response to thepresent invention. Furthermore, all documents incorporated herein byreference in their entirety are only incorporated herein to the extentthat they are not inconsistent with this specification.

The reduced alcohol or non-alcohol mouthwash and mouth rinsecompositions described herein provide an antimicrobially effectiveamount of one or more antimicrobial essential oils towards oralmicroorganisms responsible for oral malodor and the build-up of plaqueand calculus and the resulting tooth and gum diseases that may follow.

The phrase “antimicrobially effective amount” means the concentration orquantity or level of the compound of the present invention that canattain a particular medical end in having toxic activity for oralmicroorganisms.

The phrase “orally acceptable” means that the carrier is suitable forapplication to the surfaces of the oral cavity or ingestion by a livingorganism including, but not limited to, mammals and humans without unduetoxicity, incompatibility, instability, allergic response, and the like.

All percentages, parts and ratios are based upon the total weight of thecomposition of the present invention, unless otherwise specified. Allsuch weights as they pertain to the listed ingredients are based on thelevel of the particular ingredient described and, therefore, do notinclude carriers or by-products that may be included in commerciallyavailable materials, unless otherwise specified.

The phrase “reduced alcohol” or “reduced level of alcohol” indicatesthat the liquid compositions are essentially free of alcohol which meansthe liquid compositions or mouth rinses of the present invention containan amount of a C₂-C₄ monohydric alcohol of up to 10% v/v (or about 10%v/v), optionally, up to 5% v/v (or about 5% v/v), optionally, up to 1.0%v/v (or about 1.0% v/v), optionally up to 0.1% v/v (or about 0.1% v/v)by volume of the total composition. Optionally, the compositions of thepresent invention are free of C₂-C₄ monohydric alcohols.

The term “sterile water”, as used herein, means sterile water forirrigation/injection U.S.P. The USP designation means that the sterilewater for irrigation/injection is the subject of an official monographin the current (as of the filing date of this application) USPharmacopeia.

Unless otherwise specified, the phrase “oil(s) or “oily component(s)”means any hydrophobic, water immiscible compound, including but notlimited to, essential oils (such as menthol, thymol, eucalyptol andmethyl salicylate), other flavor oils, unsaturated aliphatic long chainalcohols and/or aldehydes such as 1-decen-3-ol; cis-2-nonen-1-ol,trans-2-decenal and mixtures thereof, other hydrophobic compounds suchas organic acids, vitamin E, vitamin E acetate, apigenin, triclosan andmixtures thereof and mixtures of any of the above disclosed hydrophobic,water immiscible compounds.

The terms “hydrophobic”, “hydrophobicity” or “degree of hydrophobicity”of an oil or oily component of the present invention or any mixture ofsuch oil or oily components is represented by the Octanol WaterPartition Coefficient (K_(ow)). K_(ow) is the ratio of the concentrationby weight of an oil or oily component in the octanol phase and theconcentration by weight of the oil or oily component in water phase atequilibrium and at a specified temperature for the biphasic octanol andwater system. The logarithm of K_(ow) is called the log P. Theexperimental values used to calculate the K_(ow) are typically measuredat a temperature of between 20° C. to 25° C.

Alternatively, the log P values are conveniently calculated by the “CLOG P” program, also available from Daylight CIS. This program alsolists experimental log P values when they are available in the Pomona92database. The “calculated log P” (C log P) is determined by the fragmentapproach of Hansch and Leo (cf., A. Leo, in Comprehensive MedicinalChemistry, Vol. 4, C. Hansch, P. G. Sammens, J. B. Taylor and C. A.Ramsden, Eds., p. 295, Pergamon Press, 1990, incorporated herein byreference). The fragment approach is based on the chemical structure ofeach oil or oily component, and takes into account the numbers and typesof atoms, the atom connectivity, and chemical bonding. The C log Pvalues, which is considered reliable and a widely used estimate for thisphysicochemical property, can be used instead of the experimental K_(ow)method for measuring log P values.

The higher the log P of the oil or oily component, the more hydrophobic(or, the greater the degree of hydrophobicity of) the oil or oilycomponent.

The term “turbidity” as used herein means the cloudiness or haziness ofa fluid caused by individual particles (suspended solids or liquids)that are generally invisible to the unaided eye. Fluids can containsuspended solid or liquid matter consisting of varying particle size.While some suspended material will be large enough and heavy enough tosettle rapidly to the bottom of the container (or separate into distinctlayers) if a liquid sample is left to stand, very small particles willsettle (or separate out) only very slowly or not at all if the sample isregularly agitated or the particles are colloidal. These small solid orliquid particles cause the liquid to appear turbid.

One property of such particles is that they will scatter a light beamfocused on them. This light scattering effect is considered a goodmeasure of turbidity in water. Turbidity measured this way uses aninstrument called a Turbidimeter with the detector setup to the side ofthe light beam. The more particles floating in water, the more light isscattered toward the detector and the higher the value of detectedlight. A lower value of detected light indicates a clearer or lesscloudy solution. The units of turbidity from a calibrated Turbidimeterare called Nephelometric Turbidity Units (NTUs). A clear formulation isdefined as a formulation with an NTU of less than 12 (or about 12).

First Premix Composition

The liquid or mouth rinse compositions of the present invention comprisea first premix composition.

In certain embodiments, the first premix composition includes a firstoil or oily component and a first polyol solvent.

First Oil or Oily Component

The first premix composition of the present invention comprises a firstoil or oily component, the first oil or oily component being any oil oroily component or mixture of such oil or oily components. In certainembodiments, the first oil or oily component has a log P of no less thanor greater than 2.1 (or about 2.1), optionally 2.2 (or about 2.2). Incertain embodiments such as certain mouth rinse embodiments, the firstoil or oily component of the present invention comprises at least oneantimicrobial essential oil.

Antimicrobial Essential Oils

In certain embodiments, the enhanced antimicrobial efficacy ofnon-alcohol mouth rinse compositions as described herein is attributedto the presence of minor amounts of one or more antimicrobial orbioactive essential oils (i.e. thymol, eucalyptol, menthol and methylsalicylate).

Thymol, [(CH₃)₂CHC₆H₃(CH₃)OH, also known as isopropyl-m-cresol], is onlyslightly soluble in water but is soluble in alcohol, and its presence isone of the reasons alcohol was necessary in the well-established, highalcohol commercial mouth rinses. Methyl salicylate, [C₆H₄OHCOOCH₃, alsoknown as wintergreen oil], additionally provides flavoring to thetogether with its antimicrobial function. Eucalyptol (C₁₀H₁₈O, alsoknown as cineol) is a terpene ether and provides a cooling, spicy taste.Eucalyptol may be used in place of thymol in certain formulations in thesame amount if desired. Menthol (CH₃C₆H₉(C₃H₇)OH), also known ashexahydrothymol) is also only slightly soluble in alcohol, and is fairlyvolatile. Menthol, in addition to any antiseptic properties, provides acooling, tingling sensation.

In certain embodiments, the essential oils are used in amounts effectiveto provide antimicrobial activity in the oral cavity. In specificembodiments, the total amount of essential oils present in the disclosedcompositions can be from 0.001% (or about 0.001%) to 0.35% (or about0.35%) w/v, or optionally from 0.16% (or about 0.16%) to 0.28% (or about0.28%) w/v of the composition.

In some embodiments, the compositions of the present invention containthymol and additionally eucalyptol, menthol, or methyl salicylate, ormixtures thereof. Optionally, the composition contains all four of theseessential oils.

In certain embodiments, thymol is employed in amounts of from 0.001% (orabout 0.001%) to 0.25% (or about 0.25%) w/v, or optionally from 0.04%(or about 0.04%) to 0.07% (or about 0.07%) w/v of the composition. Incertain embodiments, eucalyptol may be employed in amounts of from0.001% (or about 0.001%) to 0.11% (or about 0.11%) w/v, or optionallyfrom 0.085% (or about 0.085%) to 0.10% (or about 0.10%) w/v of thecomposition. In certain embodiments, menthol is employed in amounts offrom 0.001% (or about 0.001%) to 0.25% (or about 0.25%) w/v, oroptionally from 0.035% (or about 0.035%) to 0.05% (or about 0.05%) w/vof the composition. In certain embodiments, methyl salicylate isemployed in amounts of from 0.001% (or about 0.001%) to 0.08% (or about0.08%) w/v, or optionally from 0.04% (or about 0.04%) to 0.07% (or about0.07%) w/v of the composition.

In some embodiments, the carrier for the essential oils (the activeingredients) is typically a water-alcohol mixture, generallywater-ethanol. In the past, some antiseptic oral mouth rinsecompositions, required ethanol levels of up to about 27% v/v. These highlevels were necessary to assist the actives in providing the necessaryantimicrobial functionality as well as providing a clear, aestheticallyattractive liquid medium. Merely reducing the alcohol levels, withoutthe addition of other formulation components, results in a cloudy, lessefficacious product.

Without being bound to any theory, it is believed that in these highalcohol level oral compositions, the alcohol solubilizes theantimicrobial essential oils and in so doing acts to keep the essentialoils bioactive. The antimicrobial essential oils are more readilydispersed throughout the solution and remain free or unbound to attackpathogenic microbes throughout the oral cavity. Reducing the alcohollevels was believed to adversely affect this enhancement mechanism. Inaccordance with the present invention, however, it was surprisingly andunexpectedly found that the level of alcohol can be reduced oreliminated without sacrificing antimicrobial efficacy or clarity if themouth rinse composition contains a solvent system and surfactants astaught herein.

First Polyol Solvent

In certain embodiments, a first polyol solvent is added to the firstpremix composition. The first polyol solvent comprises a polyol orpolyhydric alcohol selected from the group consisting of polyhydricalkanes (such as propylene glycol, glycerin, butylene glycol, hexyleneglycol, 1,3-propanediol); polyhydric alkane esters (dipropylene glycol,ethoxydiglycol); polyalkene glycols (such as polyethylene glycol,polypropylene glycol) and mixtures thereof. In certain embodiments, thepolyol solvent can be present in an amount of from 0% to 20.0% (or about20.0%) w/v, optionally from 1.0% (or about 1.0%) to 15.0% (or about15.0%) w/v, or optionally from 2.5% (or about 2.5%) to 8.0% (or about8.0%) w/v of the composition.

Flavors or Flavorants

In certain embodiments, the first premix composition further comprisesflavors or flavorants may to modify or magnify the taste of the liquidcomposition or mouth rinse, or reduce or mask the sharp “bite” or “burn”of ingredients such as thymol. Suitable flavors include, but are notlimited to, oil of anise, anethole, benzyl alcohol, spearmint oil,citrus oils, vanillin and the like may be incorporated. In theseembodiments, the amount of flavor oil added to the composition can befrom 0.001% (or about 0.001%) to 1.0% (or about 1.0%) w/v, or optionallyfrom 0.01% (or about 0.010%) to 0.30% (or about 0.30%) w/v of the totalcomposition.

The particular flavors or flavorants, and other taste-improvingingredients, employed will vary depending upon the particular taste andfeel desired. Those skilled in the art can select and customize thesetypes of ingredients to provide the desired results.

Second Premix Composition

The compositions of the present invention further comprise a secondpremix composition.

In certain embodiments, the second premix composition comprises a waterinsoluble component and a second solvent or solvent system comprising,consisting of or consisting essentially of at least one polyol solvent.

Second Oil or Oily Component

The second premix composition of the present invention comprises asecond oil or oily component, the second oil or oily component being anyoil or oily component or mixture of such oil or oily components suchthat the hydrophobicity (or degree of hydrophobicity) of the second oilor oily component is less than the hydrophobicity (or degree ofhydrophobicity) of the first oil or oily component. In certainembodiments, the second oil or oily component has a log P of no morethan or less than 2.1 (or about 2.1), optionally 2.0 (or about 2.0). Incertain embodiments, the second oil or oily component of the presentinvention is or comprises at least one organic acid. In certainembodiments, the organic acid is used as a buffer or part of a bufferingsystem.

Organic Acid

Organic acids suitable for use in the compositions of the presentinvention include, but are not limited to, ascorbic acid, sorbic acid,citric acid, glycolic acid, lactic acid and acetic acid, benzoic acid,salicylic acid, phthalic acid, phenolsulphonic acid, succinic acid andmixtures thereof, optionally, the organic acid is selected from thegroup consisting of benzoic acid, sorbic acid, succinic acid, citricacid and mixtures thereof, or optionally, the organic acid is benzoicacid. In certain embodiment, the organic acid buffer is present inamounts of from 0.001% (or about 0.001% w/v) to 1.0% w/v (or about 1.0%w/v) of the composition.

When used as buffers or as part of a buffering system, the organic acidsare incorporated in amounts that maintain the pH at levels of from 3.0(or about 3.0) to 8.0 (or about 8.0), optionally from 3.5 (or about 3.5)to 6.5 (or about 6.5), optionally from 3.5 (or about 3.5) to 5.0 (orabout 5.0). Without being limited any theory, it is believed that thesepH levels provide the essential oils with an environment that alsomaximizes their antimicrobial activity and promotes stability.

In certain embodiments, the total amount of any oil or oily componentspresent in the disclosed compositions of the present invention shouldnot exceed 1.35% w/v (or about 1.35% w/v) of the total composition.Optionally, the total of all oil or oily components, can be present inan amount of from 0.04% (or about 0.04%) to 1.35% (or about 1.35%) w/v,or optionally from 0.10% (or about 0.10%) to 0.4% (or about 0.4%) w/v ofthe total composition.

Second Polyol Solvent

A second polyol solvent is added to the second premix. In certainembodiments, the second polyol solvent can be the same as or differentfrom the first polyol solvent and comprises a polyol or polyhydricalcohol selected from the group consisting of polyhydric alkanes (suchas propylene glycol, glycerin, butylene glycol, hexylene glycol,1,3-propanediol); polyhydric alkane esters (dipropylene glycol,ethoxydiglycol); polyalkene glycols (such as polyethylene glycol,polypropylene glycol) and mixtures thereof. In certain embodiments, thepolyol solvent can be present in an amount of from 1% (or about 1%) to15.0% (or about 15.0%) w/v, or optionally from 2.5% (or about 2.5%) to8.0% (or about 8.0%) w/v of the composition.

In certain embodiments, where a first polyol solvent is not added to thefirst premix, the second polyol solvent can be present in an amount offrom 1.0% (or about 1.0%) to 30.0% (or about 30.0%) w/v, or optionallyfrom 5.0% (or about 5.0%) to 15.0% (or about 15.0%) w/v of thecomposition.

Third Premix Composition

The compositions of the present invention further comprise a thirdpremix composition. In certain embodiments, the third premix compositioncomprises a surfactant and in an aqueous phase.

Surfactant

Suitable examples of surfactants useful in the compositions of thepresent invention include anionic surfactants, nonionic surfactants,amphoteric surfactants and mixtures thereof.

Anionic surfactants useful herein include, but are not limited to,sarcosine type surfactants or sarcosinates; taurates such as sodiummethyl cocoyl taurate; alkyl sulfates such as sodium trideceth sulfateor sodium lauryl sulfate; sodium lauryl sulfoacetate; sodium lauroylisethionate; sodium laureth carboxylate; sodium dodecyl benzenesulfonateand mixtures thereof. Many suitable anionic surfactants are disclosed inU.S. Pat. No. 3,959,458, to Agricola, et al., herein incorporated byreference in its entirety.

Nonionic surfactants which can be used in the compositions of thepresent invention include, but are not limited to, compounds produced bythe condensation of alkylene oxide groups (hydrophilic in nature) withan organic hydrophobic compound which may be aliphatic or alkyl-aromaticin nature. Examples of suitable nonionic surfactants include, but arenot limited to, alkyl polyglucosides; block copolymers such as ethyleneoxide and propylene oxide copolymers e.g. Poloxamers; ethoxylatedhydrogenated castor oils available commercially for example under thetrade name CRODURET (Croda Inc., Edison, N.J.); Alkyl polyethylene oxidee.g. Polysorbates, and/or; fatty alcohol ethoxylates; polyethylene oxidecondensates of alkyl phenols; products derived from the condensation ofethylene oxide with the reaction product of propylene oxide and ethylenediamine; ethylene oxide condensates of aliphatic alcohols; long chaintertiary amine oxides; long chain tertiary phosphine oxides; long chaindialkyl sulfoxides; and mixtures thereof.

The amphoteric surfactants useful in the present invention include, butare not limited to, derivatives of aliphatic secondary and tertiaryamines in which the aliphatic radical can be a straight chain orbranched and wherein one of the aliphatic sub stituents contains fromabout 8 to about 18 carbon atoms and one contains an anionicwater-solubilizing group, e.g., carboxylate, sulfonate, sulfate,phosphate, or phosphonate. Examples of suitable amphoteric surfactantsinclude, but are not limited alkylimino-diproprionates,alkylamphoglycinates (mono or di), alkylamphoproprionates (mono or di),alkylamphoacetates (mono or di), N-alkyl β-aminoproprionic acids,alkylpolyamino carboxylates, phosphorylated imidazolines, alkylbetaines, alkylamido betaines, alkylamidopropyl betaines, alkylsultaines, alkylamido sultaines, and mixtures thereof. In certainembodiments, the amphoteric surfactant is selected from the groupconsisting of alkylamidopropyl betaines, amphoacetates such as sodiumlauroamphoacetate and mixtures thereof. Mixtures of any of the abovementioned surfactants can also be employed. A more detailed discussionof anionic, nonionic and amphoteric surfactants can be found in U.S.Pat. No. 7,087,650 to Lennon; U.S. Pat. No. 7,084,104 to Martin et al.;U.S. Pat. No. 5,190,747 to Sekiguchi et al.; and U.S. Pat. No.4,051,234, Gieske, et al., each of which patents are herein incorporatedby reference in their entirety.

In certain embodiments, the liquid or mouth rinse compositions containat least one alkyl sulfate surfactant either alone or in addition to atleast one of the other above mentioned surfactants. In certainembodiments, suitable alkyl sulfate surfactants include, but are notlimited to sulfated C₈ to C₁₈, optionally sulfated C₁₀ to C₁₆ evennumbered carbon chain length alcohols neutralized with a suitable basicsalt such as sodium carbonate or sodium hydroxide and mixtures thereofsuch that the alkyl sulfate surfactant has an even numbered C₈ to C₁₈,optionally C₁₀ to C₁₆, chain length. In certain embodiments, the alkylsulfate is selected from the group consisting of sodium lauryl sulfate,hexadecyl sulfate and mixtures thereof. In certain embodiments,commercially available mixtures of alkyl sulfates are used. A typicalpercentage breakdown of alkyl sulfates by alkyl chain length incommercially available sodium lauryl sulfate (SLS) is as follows:

Alkyl Chain Length Component Percentage in SLS C₁₂ >60% C₁₄ 20%-35% C₁₆<10% C₁₀  <1% C₁₈  <1%

Suitable commercially available mixtures include Stepanol WA-100 NF USP,(Stepan, Northfield, Ill.), Texapon K12 G PH, (Texapon, Cognis, Germany)and mixtures thereof.

In certain embodiments, the amount of the alkyl sulfate surfactant addedto the composition can be from 0.05% (or about 0.05%) to 2.0% (or about2.0%) w/v, or optionally from 0.1% (or about 0.1%) to 0.5% (or about0.5%) w/v of the composition.

The total surfactant concentration should not exceed or should be lessthan 2% (or about 2%), optionally, the total surfactant concentrationshould not should not exceed or should be less than 1.5% (or about1.5%), optionally, the total surfactant concentration should not shouldnot exceed or should be less than 1.0% (or about 1.0%, optionally, thetotal surfactant concentration should not should not exceed or should beless than 0.5% (or about 0.5%).

Aqueous Phase

The first premix and the second premix are added to an aqueous phasecomprising water to form oil-in-water or water-in-oil dispersions, microemulsions or emulsions.

In certain embodiments, the aqueous phase comprises from about 60% toabout 95%, or optionally from about 75% to about 93%, by weight of thecomposition.

Alternatively, the liquid or mouth rinse compositions of the presentinvention may be formulated in a dry powder, chewing gum, semi-solid,solid or liquid concentrate form. In such embodiments, for example,water is added to q.s. as necessary in the case of liquid concentratesor powdered formulations, or water may be removed using standardevaporation procedures known in the art to produce a composition in drypowder form. Evaporated, or freeze dried forms are advantageous forstorage and shipping.

Sugar Alcohol Solvent

In certain embodiments, a sugar alcohol is also added to the liquid ormouth rinse compositions of the present invention. The sugar alcoholsolvent(s) may be selected from those multi-hydroxy-functional compoundsthat are conventionally used in oral and ingestible products. In certainembodiments, the sugar alcohol (s) should be non-metabolized andnon-fermentable sugar alcohol (s). In specific embodiments, the sugaralcohols include, but are not limited to sorbitol, xylitol, mannitol,maltitol, inositol, allitol, altritol, dulcitol, galactitol, glucitol,hexitol, iditol, pentitol, ribitol, erythritol and mixtures thereof.Optionally, the sugar alcohol is selected from the group consisting ofsorbitol and xylitol or mixtures thereof. Optionally, the sugar alcoholis sorbitol.

In certain embodiments, the total amount of sugar alcohol (s), which areadded to effectively aid in the dispersion or dissolution of the mouthrinse or other ingredients, should not exceed 20% w/v (or about 20% w/v)of the total composition. Optionally, total amount of sugar alcoholshould not exceed 17% w/v (or about 17% w/v) of the total composition.Optionally, total amount of sugar alcohol should not exceed 10% w/v (orabout 10% w/v) of the total composition. The sugar alcohol can be in anamount of from 1.0% (or about 1.0%) to 20.0% (or about 20.0%) w/v,optionally from 2.5% (or about 2.5%) to 17.0% (or about 17.0%) w/v, oroptionally from 5.0% (or about 5.0%) to 15.0% (or about 15.0%) w/v ofthe total composition.

In certain embodiments, the ratio of the sugar alcohol to the totalpolyol solvent component in the composition should be from 10:1 (orabout 10:10) to 1:10 (or about 1:10), optionally from 5:1 (or about 5:1)to 1:5 (or about 1:5), optionally 1:1 (or about 1:1) by weight.

In certain embodiments, the total amount of the solvent, including allpolyol solvents and all sugar alcohol solvents, which is added toeffectively aid in the dissolution or dispersion of the mouth rinse orother ingredients, should not exceed 47% w/v (or about 47% w/v) of thetotal composition. Optionally, total amount of solvent system should notexceed 20% w/v (or about 20% w/v) of the total composition. The solventsystem can be in an amount of from 2% (or about 2%) to 47% (or about47%) w/v, or optionally from 10% (or about 10%) to 20% (or about 20%)w/v of the total composition.

In certain embodiments, the ratio of the total solvent (i.e., polyolsolvent and the sugar alcohol solvent) to the total surfactant in thecomposition should be from 360:1 (or about 360:1) to 10:1 (or about10:1), optionally from 100:1 (or about 100:1) to 20:1 (or about 20:1) byweight.

Method of Manufacturing

Each of the above premixes is mixed until uniform and homogeneous. Onceeach premix is mixed until uniform and homogeneous, the first premix isadded to the third premix and mixed until uniform and homogeneous. Oncethe mixture of the first premix and third premix are mixed until uniformand homogeneous, the second premix is added to the mixture of the firstpremix and third premix and mixed until uniform and homogeneous.

Without being limited by theory, it is believed that first oil or oilycomponent and the second oil or oily component compete for thesurfactant and solvents in the aqueous phase of the present invention.By first mixing the first oil or oily component of higher degree ofhydrophobicity as a polyol solvent premix with an aqueous phasecontaining surfactant before adding a polyol solvent premix of thesecond oil or oily component of lower degree of hydrophobicity to theaqueous phase containing surfactant, the first oil or oily component ofhigher degree of hydrophobicity is mixed with the surfactant and/orsolvent to achieve the dispersion and/or dissolution in the aqueousphase required to produce compositions having a turbidity of less than12 (or about 12) Nephelometric Turbidity Units (NTUs). The turbidity ofthe liquid composition or mouth rinse is further reduced by adding anysugar alcohol solvents after the first and second oil or oily componentshave been added to an aqueous phase.

In certain embodiments, the liquid or mouth rinse compositions of thepresent invention have NTU values of less than 10 (or about 10),optionally 8 (or about 8), optionally 6 (or about 6), or optionally 4(or about 4).

Optional Ingredients Insoluble Particulates

In certain embodiments, the oral care compositions of the presentinvention optionally comprise a safe and effective amount of a waterinsoluble particulate. The water insoluble particulate can be anabrasive particle (such as a dentally acceptable abrasive) ornon-abrasive particulate.

In certain embodiments, dentally acceptable abrasives include, but arenot limited to, water insoluble calcium salts such as calcium carbonate,and various calcium phosphates, alumina, silica, synthetic resins andmixtures thereof. Suitable dentally acceptable abrasives may generallybe defined as those having a radioactive dentine abrasion value (RDA) offrom about 30 to about 250 at the concentrations used in thecompositions of the present invention. In certain embodiments, abrasivesare non-crystalline, hydrated, silica abrasives, particularly in theform of precipitated silica or milled silica gels availablecommercially, for example, under the trade names ZEODENT (J. M. HuberCorporation, Edison, N.J.), and SYLODENT (W.R. Grace & Co., New York,N.Y.), respectively. In certain embodiments, the compositions accordingto the present invention comprise from about 1% to about 20%, or,optionally, from about 5% to about 10% by weight of the abrasive.

Alternatively, the insoluble particulate is a non-abrasive particulatewhich is visible to the unaided eye and stable in the compositions ofthe present invention.

The non-abrasive particulate can be of any size, shape, or color,according to the desired characteristic of the product. The non-abrasiveparticulates will typically have the shape of a small round orsubstantially round ball or sphere, however, platelet or rod-shapedconfigurations are also contemplated herein. Generally, a non-abrasiveparticulate has an average diameter of from about 50 μm to about 5000μm, optionally from about 100 μm to about 3000 μm, or optionally fromabout 300 μm to about 1000 μm. By the terms “stable” and/or “stability”,it is meant that the abrasive or non-abrasive particulates are notdisintegrated, agglomerated, or separated under normal shelf conditions.In certain embodiments, the terms “stable” and/or “stability” furthermean that the compositions of present invention contain no visible orminimally visible (to the unaided eye) signs of sedimentation of theinsoluble particulates after 8 weeks, optionally 26 weeks, optionally 52weeks, at room temperature.

The non-abrasive particulates herein are typically incorporated in thepresent compositions at levels of from about 0.01% to about 25%,optionally, from about 0.01% to about 5%, or optionally, from about0.05% to about 3%, by weight of the composition.

The non-abrasive particulate herein will typically comprise a structuralmaterial and/or, optionally, an encompassed material.

The structural material provides a certain strength to the non-abrasiveparticulates so that they retain their distinctively detectablestructure in the compositions of the present invention under normalshelf conditions. In one embodiment, the structural material further canbe broken and disintegrated with very little shear on the teeth, tongueor oral mucosa upon use.

The non-abrasive particulates can be solid or liquid, filled orun-filled, as long as they are stable in the compositions of the presentinvention. The structural material used for making the non-abrasiveparticulates varies depending on the compatibility with othercomponents, as well as material, if any, to be encompassed in thenon-abrasive particulates. Exemplary materials for making thenon-abrasive particulates herein include: polysaccharide and saccharidederivatives such as crystalline cellulose, cellulose acetate, celluloseacetate butyrate, cellulose acetate phthalate, cellulose nitrate,ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose,hydroxypropylmethylcellulose phthalate, methyl cellulose, sodiumcarboxymethylcellulose, gum acacia (gum arabic), agar, agarose,maltodextrin, sodium alginate, calcium alginate, dextran, starch,galactose, glucosamine, cyclodextrin, chitin, amylose, amylopectin,glycogen, laminaran, lichenan, curdlan, inulin, levan, pectin, mannan,xylan, alginic acid, arabic acid, glucommannan, agarose, agaropectin,prophyran, carrageenen, fucoidan, glycosaminoglycan, hyaluronic acid,chondroitin, peptidoglycan, lipopolysaccharide, guar gum, starch, andstarch derivatives; oligosaccharides such as sucrose, lactose, maltose,uronic acid, muramic acid, cellobiose, isomaltose, planteose,melezitose, gentianose, maltotriose, stachyose, glucoside andpolyglucoside; monosaccharides such as glucose, fructose, and mannose;synthetic polymers such as acrylic polymers and copolymers includingpolyacrylamide, poly(alkyl cyanoacrylate), and poly(ethylene-vinylacetate), and carboxyvinyl polymer, polyamide, poly(methyl vinylether-maleic anhydride), poly(adipyl-L-lysine), polycarbonate,polyterephthalamide, polyvinyl acetate phthalate,poly(terephthaloyl-L-lysine), polyarylsulfone, poly(methylmethacrylate),allyl methacrylate, poly(ε-caprolactone), polyvinylpyrrolidone,polydimethylsiloxane, polyoxyethylene, polyester, polyglycolic acid,polylactic acid, polyglutamic acid, polylysine, polystyrene,poly(styrene-acrylonitrile), polyimide, and poly(vinyl alcohol); andother material such as fat, fatty acid, fatty alcohol, milk solids,molasses, gelatin, gluten, albumin, shellac, caseinate, bees wax,carnauba wax, spermaceti wax, hydrogenated tallow, glycerolmonopalmitate, glycerol dipalmitate, hydrogenated castor oil, glycerolmonostearate, glycerol distearate, glycerol tristearate,12-hydroxystearyl alcohol, protein, and protein derivatives; andmixtures thereof. Components herein may be described in other sectionsas useful components for the present composition. In certainembodiments, the components as described in this section form thestructure of the non-abrasive particulates so as to not be substantiallydissolved or dispersed from the particulates and into the compositionsof the present invention under normal shelf conditions.

In other embodiments, the structural material herein comprisescomponents selected from the group consisting of polysaccharides andtheir derivatives, saccharides and their derivatives, oligosaccharides,monosaccharides, and mixtures thereof, or optionally, comprisescomponents are having various degrees of water solubility. In someembodiments, the structural material comprises lactose, cellulose, andhydroxypropyl methylcellulose.

Suitable non-abrasive particulates also include organogel particles asdescribed in detail in U.S. Pat. No. 6,797,683. Non-abrasiveparticulates that are organogel particles typically comprise astructural material selected from waxes (e.g., beeswax, paraffin,water-insoluble wax, carbon-based wax, silicone wax, microcrystallinewax, etc.), triglycerides, acid triglycerides, polymers, fluoroalkyl(meth)acrylate polymers and copolymers, acrylate polymers,ethylene/acrylate copolymers, polyethylene, polypropylene polymers andcopolymers, fatty acids, fatty alcohols, fatty acid esters, fatty acidethers, fatty acid amides, alkylene polyhydric alcohols, fatty acidamide of an alkanolamine, glyceryl monostearate,(aryl-substituted)sugars, dibenzyl sorbitol (or mannitoal, rabbitol,etc.), condensates and precondensates of lower monohydric alcohols,trihydroic alcohols, lower polyglycols, propylene/ethylenepolycondensates, and the like. Optionally, structural material fornon-abrasive particulates that are organogel particles include beeswax,carnauba wax, low molecular weight ethylene homopolymers (e.g. Polywax500, Polywax 1000, or Polywax 2000 polyethylene materials available fromBaker Petrolite Corp.), or paraffin wax.

The non-abrasive particulates herein may encompass, contain, or befilled with an encompassed material. Such encompassed material can bewater soluble or water insoluble. Suitable encompassed materials includebenefit agents as described herein such as: oral care actives, vitamins,pigments, dyes, antimicrobial agents, chelating agents, opticalbrighteners, flavors, perfumes, humectants, minerals, and mixturesthereof. The encompassed materials herein are substantially retainedwithin the non-abrasive particulates, and are substantially notdissolved from the particulates and into the compositions of the presentcomposition under normal shelf conditions.

Particularly useful commercially available non-abrasive particulatesherein are those with tradenames Unisphere and Unicerin available fromInduchem AG (Switzerland), and Confetti Dermal Essentials available fromUnited-Guardian Inc. (NY, USA). Unisphere and Unicerin particles aremade of microcrystalline cellulose, hydroxypropyl cellulose, lactose,vitamins, pigments, and proteins. Upon use, the Unisphere and Unicerinparticles can be disintegrated with very little shear and withpractically no resistance, and readily disperse in the compositions ofthe present invention.

Suitable non-abrasive particulates for incorporation in the presentcompositions are described in detail in U.S. Pat. No. 6,797,683(organogel particles); U.S. Pat. No. 6,045,813 (rupturable beads); U.S.2004/0047822 A1 (visible capsules); and U.S. Pat. No. 6,106,815(capsulated or particulated oily substances), each of which patentdocuments are herein incorporated by reference in their entirety.

In certain embodiments, the abrasive and/or nonabrasive particles have adensity different or, optionally, substantially different from thecarrier in which these particles are formulated.

Fluoride Releasing Compounds

In certain embodiments, fluoride providing compounds may be present inthe mouth rinse compositions of this invention. These compounds may beslightly water soluble or may be fully water soluble and arecharacterized by their ability to release fluoride ions or fluoridecontaining ions in water. Typical fluoride providing compounds areinorganic fluoride salts such as soluble alkali metal, alkaline earthmetal, and heavy metal salts, for example, sodium fluoride, potassiumfluoride, ammonium fluoride, cupric fluoride, zinc fluoride, stannicfluoride, stannous fluoride, barium fluoride, sodium hexafluorosilicate,ammonium hexafluorosilicate, sodium fluorozirconate, sodiummonofluorophosphate, aluminum mono-and difluorophosphate and fluorinatedsodium calcium pyrophosphate. Amine fluorides, such asN′-octadecyltrimethylendiamine-N,N,N′-tris(2-ethanol)-dihydrofluorideand 9-octadecenylamine-hydrofluoride), may also be used.

In certain embodiments, the fluoride providing compound is generallypresent in an amount sufficient to release up to 0.15% (or about 0.15%),optionally 0.001% (or about 0.001%) to 0.1% (or about 0.1%), optionallyfrom 0.001% (or about 0.001%) to 0.05% (or about 0.05%) fluoride byweight of the composition.

Zinc Salts

In certain embodiments, zinc salts such as zinc chloride, zinc acetateor zinc citrate may be added as an astringent for an “antisepticcleaning” feeling, as a breath protection enhancer or as anticalculusagent in an amount of from 0.0025% w/v (or about 0.0025% w/v) to 0.1%w/v (or about 0.1% w/v) of the composition.

Sensitivity Reducing Agents

In certain embodiments, sensitivity reducing agents, namely potassiumsalts of nitrate and oxalate in an amount from 0.1% (or about 0.1%) to5.0% (or about 5.0%) w/v of the composition may be incorporated into thepresent invention. Other potassium releasing compounds are feasible(e.g. KCl). High concentrations of calcium phosphates may also providesome added sensitivity relief. These agents are believed to work byeither forming an occlusive surface mineral deposit on the tooth surfaceor through providing potassium to the nerves within the teeth todepolarize the nerves. A more detailed discussion of suitablesensitivity reducing can be found in US 20060013778 to Hodosh and U.S.Pat. No. 6,416,745 to Markowitz et al., both of which are hereinincorporated by reference in their entirety.

Anticalculus Agents

In certain embodiments, compounds with anti-calculus benefits (e.g.polyphosphates, phosphonates, various carboxylates, polyaspartic acid,inositol phosphate etc.) may be incorporated into the present invention.Also useful as an anticalculus agent are the anionic polymericpolycarboxylates. Such materials are well known in the art, beingemployed in the form of their free acids or partially or preferablyfully neutralized water soluble alkali metal (e.g. potassium andpreferably sodium) or ammonium salts. Preferred are 1:4 to 4:1 by weightcopolymers of maleic anhydride or acid with another polymerizableethylenically unsaturated monomer, preferably methyl vinyl ether(methoxyethylene) having a molecular weight (M.W.) of about 30,000 toabout 1,000,000. These copolymers are available for example as GantrezAN 139 (M.W. 500,000), AN 119 (M.W. 250,000) and preferably S-97Pharmaceutical Grade (M.W. 70,000), of GAF Chemicals Corporation.

Additional Ingredients

Although the liquid or mouth rinse compositions of the present inventionmay be formulated to be substantially clear and/or colorless to theunaided eye, acceptably approved food dyes are preferably used toprovide a pleasing color to the compositions of the invention. These maybe selected from, but not limited to, the long list of acceptable fooddyes. Suitable dyes for this purpose include FD&C yellow #5, FD&C yellow#10, FD&C blue #1 and FD&C green #3. These are added in conventionalamounts, typically in individual amounts of from 0.00001% w/v (or about0.00001% w/v) to 0.0008% w/v (or about 0.0008% w/v), optionally from0.00035% w/v (or about 0.00035% w/v) to 0.0005% w/v (or about 0.0005%w/v) of the composition.

Other conventional ingredients may be used in the liquid or mouth rinsecompositions of this invention, including those known and used in theart. Examples of such ingredients include thickeners, suspending agentsand softeners. Thickeners and suspending agents useful in thecompositions of the present invention can be found in U.S. Pat. No.5,328,682 to Pullen et al., herein incorporated by reference in itsentirety. In certain embodiments, these are incorporated in amounts offrom 0.1% w/v (about 0.1% w/v) to 0.6% w/v (or about 0.6% w/v),optionally 0.5% w/v (or about 0.5% w/v) of the composition.

A more detailed description of useful oral care actives and/or inactiveingredients and further examples thereof can be found in U.S. Pat. No.6,682,722 to Majeti et al. and U.S. Pat. No. 6,121,315 to Nair et al.,each of which are herein incorporated by reference in its entirety.

In certain embodiments, the compositions of the present invention arefree of or essentially free of bioavailability affecting compounds. Asused herein, “bioavailability affecting compound”, means compounds thatnegatively affect the bioavailability of any incorporated essential oilssuch as by binding the essential oils or otherwise inactivating theessential oils. “Essentially free” as used with respect tobioavailability affecting compounds is defined as formulations havingless than 5% (or about 5%), optionally, 3% (or about 3%), optionally, 1%(or about 1%), or optionally 0.1, or optionally, 0.01% (or about 0.01%),by weight (w/v) of the total composition of a bioavailability affectingcompound. In certain embodiments, the bioavailability affecting compoundcan include, but is not limited to, polyethylene oxide/polypropyleneoxide block copolymers such as poloxamers; cyclodextrins; polysorbatessuch as Tweens; and mixtures thereof.

Methods of Practicing the Present Invention

The invention illustratively disclosed herein may be practiced in theabsence of any component, ingredient, or step which is not specificallydisclosed herein.

In certain embodiments, the compositions of the present invention areapplied to teeth and/or soft surfaces of the oral cavity for at leasttwo consecutive applications, optionally, at least (or greater than) 3(or about 3) or optionally, at least (or greater than) 5 (or about 5)consecutive applications.

When applied to teeth and/or soft surfaces of the oral cavity, incertain embodiments, the composition is allowed to remain in contactwith the teeth and/or soft surfaces of the oral cavity for at least (orgreater than) 10 (or about 10) seconds, optionally 20 (or about 20)seconds, optionally 30 (or about 30) seconds, optionally 50 (or about50) seconds, or optionally 60 (or about 60) seconds.

Various embodiments of the invention have been set forth above. Eachembodiment is provided by way of explanation of the invention, notlimitation of the invention. In fact, it will be apparent to thoseskilled in the art that various modifications and variations can be madein the present invention without departing from the scope or spirit ofthe invention. For instance, features illustrated or described as partof one embodiment, can be used on another embodiment to yield a stillfurther embodiment. Thus, it is intended that the present inventioncover such modifications and variations as come within the scope of theappended claims and their equivalents.

EXAMPLES

The following examples are illustrative only and should not be construedas limiting the invention in any way. Those skilled in the art willappreciate that variations are possible which are within the spirit andscope of the appended claims.

Example 1: Effect of Various Methods of Forming Formulations, andIncreasing Surfactant Levels

Nine propylene-glycol based mouth rinse formulations were prepared by avariety of methods using various surfactants that are approved for usein oral care products. The formulations were tested for turbidity andantimicrobial activity. Turbidity was tested using a LaboratoryTurbidimeter Model 2100N from Hach Company (Loveland, Colo.). Theformulations were also tested using an in-vitro single species S. mutansbiofilm model. A 22-hour S. mutans biofilm was grown (N=96) and exposedto the formulations as well as positive and negative controls for 30seconds. Sterile water was used as the negative control. After treatmentthe biofilm was neutralized and rinsed. The biofilm was harvested viasonication using a Misonix XL-2000 Ultrasonic processor (Qsonica, LLC,Newtown, Conn.). Using a Celsis Rapid Detection RapiScreen kit (CelsisInternational PLC, Chicago). The bacteria was lysed with Celsis Luminexand the ATP from the bacteria was measured using the bioluminescencemarker Celsis LuminATE. Decreasing log RLUs (relative light units)indicates fewer bacteria alive after treatment. The nine formulationsare shown on Table 1. Final formulations were adjusted to pH 4.2 with0.1M NaOH or 0.1M HCl if necessary.

TABLE 1 Formulations 1A 1B 1C 1D 1E 1F 1G 1H 1I Negative Ingredients (%w/w) (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) (% w/w)Control Propylene 7.0  7.0  7.0  7.0  7.0  7.0  7.0  7.0  7.0  — glycolUSP L-Menthol  0.0413  0.0413  0.0413  0.0413  0.0413  0.0413  0.0413 0.0413  0.0413 — USP Thymol NF  0.0620  0.0620  0.0620  0.0620  0.0620 0.0620  0.0620  0.0620  0.0620 — Methyl  0.0641  0.0641  0.0641  0.0641 0.0641  0.0641  0.0641  0.0641  0.0641 — salicylate NF Eucalyptol 0.0895  0.0895  0.0895  0.0895  0.0895  0.0895  0.0895  0.0895  0.0895— USP Flavor  0.1000  0.1000  0.1000  0.1000  0.1000  0.1000  0.1000 0.1000  0.1000 — Sorbitol 10.000  10.000  10.000  10.000  10.000 10.000  10.000  10.000  10.000  — (70% solu- tion) USP Sodium  0.3150 0.3150  0.3150 — —  0.3150  0.3150  0.3150  0.3150 — Lauryl Sulfate USPPoloxamer — — —  2.0000 — — — — — — 407 NF Tween 20 — — — —  2.0000 — —— — — Sodium  0.0606  0.0606  0.0606  0.0606  0.0606  0.0606  0.0606 0.0606  0.0606 — Saccharin USP Sucralose NF  0.0100  0.0100  0.0100 0.0100  0.0100  0.0100  0.0100  0.0100  0.0100 — Benzoic  0.0859 0.0859  0.0859  0.0859  0.0859  0.0859  0.0859  0.0859  0.0859 — AcidUSP Sodium  0.0773  0.0773  0.0773  0.0773  0.0773  0.0773  0.0773 0.0773  0.0773 — Benzoate NF FD&C  0.00002  0.00002  0.00002  0.00002 0.00002  0.00002  0.00002  0.00002  0.00002 — Green #3 Purified QS QSQS QS QS QS QS QS QS — Water USP TOTAL 100.0   100.0 100.0 100.0 100.0100.0 100.0 100.0 100.0 — log RLU 6.01  5.46  5.45  7.64  7.68  5.49 5.62  5.52  5.55  7.67 M-factor 1.66  2.21  2.22  0.03  -0.01  2.18 2.05  2.15  2.12  0   Turbidity 11.4   13.3   12.8   10.7   2.22  16.1  3.93  15.9   17.2   (NTU)

The procedure for mixing the formulations was as follows:

Formulation 1A: The water was put in an appropriately sized tank (orvessel), then all remaining ingredients were added to the water andmixed until dispersed. No separate premixes were formed.

Formulation 1B: In step 1, the polyol solvent (i.e., propylene glycol)was put in an appropriately sized tank (or vessel). The active oils andflavor were added to the polyol solvent in the tank and mixed untilhomogeneous and uniform to form a premix. In step 2, instead of addingas the final component in the final step of the formulation process, thesugar alcohol was added to the premix and mixed until the formulationwas homogeneous and uniform before adding the surfactant, water, organicacid buffer, preservative, sweeteners and dyes. In step 3, thesurfactant was added to the premix and mixed until the formulation washomogeneous and uniform. In step 4, the water was added to the premixand mixed until the formulation was homogeneous and uniform. In step 5,the organic acid buffer, preservative, and sweeteners were added to thepremix, and mixed until homogeneous and uniform. In step 6, the dye wasadded to the premix and mixed until the formulation was homogeneous anduniform.

Formulations 1C, 1D, and 1E: In step 1, the polyol solvent (i.e.,propylene glycol) was put in an appropriately sized tank (or vessel).The organic acid buffer was added to the polyol solvent to form a firstpremix and mixed until homogeneous and uniform. In step 2, instead offorming a second premix of active oil and a second polyol solvent andadding the second premix to a third premix comprising water, surfactant,preservative and sweetener, the active oils and flavor were addeddirectly to the first premix and mixed until homogeneous and uniform. Instep 3, the sugar alcohol co-solvent was added to the first premix andmixed until the formulation was homogeneous and uniform. In step 4, thesurfactant was added to the first premix and mixed until the formulationwas homogeneous and uniform. In step 5, the water, sweeteners, andpreservative were added to the first premix, and mixed until homogeneousand uniform. In step 6, the dye was added to the first premix and mixeduntil the formulation was homogeneous and uniform. In Formulations 1Dand 1E, higher levels of surfactant were added, when compared toFormulation 1C.

Formulation 1F: In step 1, in a first appropriately sized tank (orvessel), a first premix was formed by adding 5% first polyol solvent(i.e., propylene glycol) to active oils and flavor and mixed until theywere homogeneous and uniform. In step 2, in a second appropriately sizedtank (or vessel), a second premix was formed by adding 2.0% secondpolyol solvent which was the same as the first polyol solvent to anorganic acid buffer and mixed in the second tank until homogeneous anduniform. In step 3, instead of adding as the final component in thefinal step of the formulation process, the sugar alcohol solvent wasadded and mixed directly into the first premix until homogeneous anduniform before adding the surfactant, water, preservative, sweetenersand dyes. In step 4, the surfactant was added and mixed into the firstpremix until the formulation was homogeneous and uniform. In step 5, thewater was added and mixed into the first premix until the formulationwas homogeneous and uniform. In step 6, the second premix was added tothe first premix and mixed until the formulation was homogeneous anduniform. In step 7, the preservative and sweeteners were added, andmixed until homogeneous and uniform. In step 8, the dye was added andmixed until the formulation was homogeneous and uniform.

Formulation 1G (using the inventive process): In step 1, in a firstappropriately sized tank (or vessel), a premix was formed by adding 5.0%first polyol solvent (i.e., propylene glycol), active oils and flavorand mixed until homogeneous and uniform. In step 2, in a secondappropriately sized tank (or vessel), a second premix was formed byadding to an organic acid buffer 2.0% second polyol solvent which wasthe same as the first polyol solvent and mixed until homogeneous anduniform. In step 3, in a third appropriately sized tank (or vessel), athird premix was formed by adding surfactant, preservative andsweeteners to water and mixing until homogeneous and uniform. In step 4,the first premix was added to the third premix and mixed untilhomogeneous and uniform. In step 5, the second premix was added to themixture of the first and third premixes and mixed until homogeneous anduniform. In step 6, the dye was added to the mixture of the threepremixes and mixed until homogeneous and uniform. In step 7, the sugaralcohol was added as the final component to the mixture of the threepremixes and mixed until the final mixture was homogeneous and uniform.

Formulation 1H: In step 1, in a first appropriately sized tank (orvessel), instead of forming separate premixes (one premix containing theactive oils and the other premix containing the organic acid buffer), afirst premix was formed by adding both organic acid buffer and activeoils to a polyol solvent (i.e., propylene glycol) and flavor and mixinguntil homogeneous and uniform. In step 2, in a second appropriatelysized tank (or vessel), instead of adding as the final component in thefinal step of the formulation process, the sugar alcohol solvent wasadded to surfactant, preservative, sweeteners and water and mixed untilhomogeneous and uniform to form a second premix. In step 3, the firstpremix was added to the second premix and mixed until homogeneous anduniform. In step 4, the dye was added to the mixture of the two premixesand mixed until homogeneous and uniform.

Formulation 1I: In step 1, in a first appropriately sized tank (orvessel), a first premix was formed by adding 5.0% first polyol solvent(i.e., propylene glycol) to active oils and flavor and mixed untilhomogeneous and uniform. In step 2, in a second appropriately sized tank(or vessel), a second premix was formed by adding 2.0% second polyolsolvent which was the same as the first polyol solvent to an organicacid buffer and mixed until homogeneous and uniform. In step 3, a thirdappropriately sized tank (or vessel), a third premix was formed byadding surfactant, sorbitol, preservative and sweeteners water andmixing until homogeneous and uniform. In step 4, instead of adding thefirst premix to the third premix, the second premix was added to thethird premix and mixed until homogeneous and uniform. In step 5, thefirst premix is added to the mixture of the second premix and thirdpremix and mixed until homogeneous and uniform. In step 6, the dye wasadded and mixed until uniform.

In addition to the listing the formulation ingredients, Table 1 showsthe results of the turbidity test, in Nephelometric Turbidity Units(NTU), and S. mutans biofilm kill tests, in log RLU and M-Factor units.A typical M-factor for a commercially available alcohol containingessential oil mouth rinse is about 1.87 (log RLU of 5.8) in this model.

Table 1 also shows that all formulations containing sodium laurylsulfate (Formulations 1A, 1B, 1C and 1F through 1I) displayed highbiocidal activity (M-factor between 1.66 and 2.22). However, theturbidity of all of three sodium lauryl sulfate formulations (1A, 1B,and 1C) was high (NTU greater than about 10.5). When the totalsurfactant concentration level was raised to 2.0% (Formulations 1D and1E), the turbidity improved, however, at such a high surfactantconcentration level, the biocidal activity, as measured by M-factor,decreased substantially (M-factor=0.03 and −0.01, respectively). Onlythe formulation formed by the inventive processes of the presentinvention (Formulation 1G) provided both good efficacy (M-factor=2.05)and the lowest turbidity (NTU less than 4.0).

What is claimed is:
 1. A composition comprising: a. polyol solventselected from the group consisting of polyhydric alkanes, polyhydricalkane esters, polyalkene glycols, and mixtures thereof; b. sugaralcohol solvent selected from the group consisting of sorbitol, xylitol,mannitol, maltitol, inositol, allitol, altriol, dulcitol, galactitol,glucitol, hexitol, iditol, pentitol, ribitol, erythritol, and mixturesthereof; c. surfactant selected from the group consisting of anionicsurfactants, nonionic surfactants, amphoteric surfactants and mixturesthereof. d. organic acid selected from the group consisting of benzoicacid, sorbic acid, succinic acid, citric acid, and mixtures thereof; e.one or more antimicrobial essential oils; and f. water; wherein saidcomposition is free of C₂-C₄ monohydric alcohols.
 2. The composition ofclaim 1 wherein said polyol solvent comprises propylene glycol.
 3. Thecomposition of claim 1 wherein said sugar alcohol solvent comprisessorbitol.
 4. The composition of claim 1 wherein said surfactantcomprises sodium lauryl sulfate.
 5. The composition of claim 1 whereinsaid surfactant comprises a Poloxamer surfactant.
 6. The composition ofclaim 1 wherein said organic acid comprises benzoic acid.
 7. Thecomposition of claim 1 wherein said one or more antimicrobial essentialoils are selected from the group consisting of menthol, thymol,eucalyptol, methyl salicylate and combinations of two or more thereof.8. The composition of claim 1 comprising propylene glycol, sorbitol, andPoloxamer
 407. 9. The composition of claim 8 further comprising sodiumlauryl sulfate.
 10. The composition of claim 9 wherein said one or moreantimicrobial essential oils are selected from the group consisting ofmenthol, thymol, eucalyptol, methyl salicylate and combinations of twoor more thereof.